# Association Between Polygenic Risk Scores and Treatment Response to Antidepressants, Benzodiazepines, and Antihistamines in Anxiety and Depression

## TL;DR

This study explores how genetic risk scores can predict responses to anxiety and depression treatments like antidepressants, benzodiazepines, and antihistamines.

## Contribution

The study introduces the use of polygenic risk scores to predict treatment response to specific anxiety and depression medications.

## Key findings

- PRS for depression predicted benzodiazepine monotherapy with an odds ratio of 1.29.
- PRS for anxiety and schizophrenia predicted antihistamine monotherapy with odds ratios of 1.25 and 1.24, respectively.
- No PRS significantly predicted antidepressant monotherapy response.

## Abstract

Anxiety and depression are the most prevalent mental health disorders. The first-line treatment is antidepressants, such as serotonin reuptake inhibitors, but benzodiazepines and antihistamines are also used to treat anxiety. Only one-third of patients achieve remission with first-line treatment. Identifying responders and nonresponders to monotherapy prior to treatment could increase remission rates and reduce dropout. The aim of the current study was to predict response to antidepressants, benzodiazepines, and antihistamines from polygenic risk scores (PRSs) in individuals with anxiety and/or depression symptoms.

We identified 2515 individuals in a genotyped cohort in the Swedish Twin Registry who had been prescribed drugs for anxiety and/or depression. Of these individuals, 1037 received monotherapy (555 with antidepressants, 169 with benzodiazepines, and 313 with antihistamines). The remaining 1478 individuals switched or added more drugs during the assessment period (2005–2018). The accuracy of 42 PRSs for psychiatric diagnoses as well as for nonclinical phenotypes in predicting mono- versus multitherapy was assessed using logistic regression.

Monotherapy with benzodiazepines was predicted by a PRS for depressive symptoms indexed by the Patient Health Questionnaire (odds ratio [OR] = 1.29), while monotherapy with antihistamines was predicted by a PRS for lifetime anxiety disorder (OR = 1.25) and a PRS for schizophrenia (OR = 1.24). None of the investigated PRSs significantly predicted monotherapy with antidepressants.

Real-world data suggest that monotherapy with benzodiazepines or antihistamines can be predicted from PRSs related to anxiety, depression, and schizophrenia.

The study investigated how genetic factors measured by polygenic risk scores (PRSs) predict treatment response to antidepressants, benzodiazepines, and antihistamines for anxiety and depression. The researchers analyzed data from 2515 genotyped individuals in a large twin registry and linked the PRSs to single- and multiple-drug treatments. PRSs related to depression, anxiety, and schizophrenia predicted responses to benzodiazepines and antihistamines but not antidepressants. These findings suggest that genetic insights could help personalize treatments, thereby enhancing efficacy and reducing trial and error in prescribing.

The study investigated how genetic factors measured by polygenic risk scores (PRSs) predict treatment response to antidepressants, benzodiazepines, and antihistamines for anxiety and depression. The researchers analyzed data from 2515 genotyped individuals in a large twin registry and linked the PRSs to single- and multiple-drug treatments. PRSs related to depression, anxiety, and schizophrenia predicted responses to benzodiazepines and antihistamines but not antidepressants. These findings suggest that genetic insights could help personalize treatments, thereby enhancing efficacy and reducing trial and error in prescribing.